Dendritic cell CTLA-4⁺ extracellular vesicles as regulators of T cell polarization

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B630
Abstract ID: 6298

Presenting Author:
Nalini Bisht , Graduate student at Baylor Col. of Med., Duncan Comp. Cancer Ctr., Baylor Col. of Med.

Abstract:

Dendritic cells (DC) are professional antigen-presenting cells that prime de novo T cell responses. DC release extracellular vesicles (EV) to communicate environmental context to other cells of the immune system. Our published data demonstrate that CTLA-4 is expressed on the outer surface of DC-secreted EV. DC-released CTLA-4⁺ EV are internalized by bystander DC and result in downregulation of costimulatory B7 expression on these bystander DC. T_H2 polarization of DC results in enhanced secretion of CTLA-4⁺ EV as compared to T_H1 polarized DC which abrogate secretion of CTLA-4⁺ EV almost entirely. Furthermore, knockdown of CTLA-4 in DC resulted in upregulated CD8⁺ T-cell proliferation and enhanced antitumor immunity. Here we report additional characterization of how DC-derived EV modulate adaptive immunity. Co-culture of CTLA-4^neg EV with naïve T cells induced significant T cell blast formation and enhanced effector functionality of T cells in the form of upregulated granzyme B and IFN-g in comparison to naïve T-cells cultured with CTLA-4⁺ EV, indicative of a T_H1 response. Additionally, CTLA-4^neg EV downregulated Treg proliferation compared to CTLA-4⁺ EV. These data support the hypothesis that DC CTLA-4⁺ EV are important effector vehicles through which DC propagate T_H polarization signals. Future investigations will determine the therapeutic application of the EV-stimulated T cells, and the corresponding transcriptional changes induced.